Efficacy and safety of adjunctive padsevonil in adults with drug-resistant focal epilepsy: Results from two double-blind, randomized, placebo-controlled trials
| Autor: | Michael, Rademacher, Manuel, Toledo, Wim, Van Paesschen, Kore K, Liow, Ivan G, Milanov, Maria-Luise, Esch, Nan, Wang, Merran, MacPherson, William J, Byrnes, Timothy D C, Minh, Elizabeth, Webster, Konrad J, Werhahn |
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| Přispěvatelé: | Institut Català de la Salut, [Rademacher M] Department of Epileptology, University of Bonn Medical Center, Bonn, Germany. [Toledo M] Unitat d’Epilèpsia, Servei de Neurologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Van Paesschen W] Department of Neurology, University Hospitals Leuven, Leuven, Belgium. [Liow KK] Comprehensive Epilepsy Center, Hawaii Pacific Neuroscience, Honolulu, Hawaii, USA. [Milanov IG] Medical University of Sofia, Sofia, Bulgaria. [Esch ML] UCB Pharma, Monheim am Rhein, Germany, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Adult
Drug Resistant Epilepsy fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos [FENÓMENOS Y PROCESOS] Clinical Neurology administración de los servicios de salud::calidad de la atención sanitaria::evaluación de resultados y procesos (atención a la salud)::evaluación del desenlace (asistencia sanitaria)::resultado del tratamiento [ATENCIÓN DE SALUD] Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Epilepsy [DISEASES] Anticonvulsius - Ús terapèutic antiepileptic drug Seizures dual mechanism of action Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Drug Resistance [PHENOMENA AND PROCESSES] Humans acciones y usos químicos::acciones farmacológicas::usos terapéuticos::fármacos del sistema nervioso central::anticonvulsivantes [COMPUESTOS QUÍMICOS Y DROGAS] antiseizure medication tolerability Resistència als medicaments Science & Technology Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Central Nervous System Agents::Anticonvulsants [CHEMICALS AND DRUGS] Neurosciences synaptic vesicle protein 2 focal seizure Epilèpsia - Tractament Treatment Outcome Neurology Avaluació de resultats (Assistència sanitària) enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::epilepsia [ENFERMEDADES] Anticonvulsants Drug Therapy Combination SEIZURES Epilepsies Partial Neurosciences & Neurology Neurology (clinical) Life Sciences & Biomedicine Health Services Administration::Quality of Health Care::Outcome and Process Assessment (Health Care)::Outcome Assessment (Health Care)::Treatment Outcome [HEALTH CARE] |
| Zdroj: | Scientia |
| Popis: | Antiepileptic drug; Antiseizure medication; Tolerability Fármaco antiepiléptico; Medicamento anticonvulsivo; Tolerabilidad Medicament antiepilèptic; Medicament anticonvulsiu; Tolerabilitat Objective To characterize efficacy, safety/tolerability, and pharmacokinetics of padsevonil (PSL) administered concomitantly with ≤3 antiseizure medications (ASMs) for observable focal seizures in adults with drug-resistant epilepsy in two multicenter, randomized, double-blind, placebo-controlled, parallel-group trials. Methods The phase 2b dose-finding trial (EP0091/NCT03373383) randomized patients 1:1:1:1:1 to PSL 50/100/200/400 mg or placebo twice daily (b.i.d.). The phase 3 efficacy trial (EP0092/NCT03739840) randomized patients 1:1:1:1 to PSL 100/200/400 mg or placebo b.i.d. Patients with observable (focal aware with motor symptoms, focal impaired awareness, focal to bilateral tonic–clonic) focal seizures for ≥3 years, experiencing them ≥4 times per 28 days including during the 4-week baseline period despite treatment with ≥4 lifetime ASMs including current ASMs, were enrolled. Results In EP0091 and EP0092, 410 and 231 patients, respectively, were randomized and received at least one dose of trial medication. In patients in EP0091 on PSL 50/100/200/400 mg b.i.d. (n = 80/82/81/81, respectively) versus placebo (n = 81), outcomes included percentage reductions over placebo in observable focal seizure frequency during the 12-week maintenance period: 17.2%, 19.1% (p = 0.128), 19.2% (p = 0.128), 12.4% (p = 0.248); 75% responder rates (p-values for odds ratios): 13.8%, 12.2% (p = 0.192), 11.1% (p = 0.192), 16.0% (p = 0.124) versus 6.2%; 50% responder rates: 33.8% (p = 0.045), 31.7% (p = 0.079), 25.9% (p = 0.338), 32.1% (p = 0.087), versus 21.0%; TEAEs were reported by 82.7% (67/81), 78.3% (65/83), 74.4% (61/82), 90.1% (73/81) versus 78.3% (65/83). In patients in EP0092 on PSL 100/200/400 mg b.i.d. (n = 60/56/56, respectively) versus placebo (n = 54), outcomes included percentage reductions over placebo: −5.6% (p = 0.687), 6.5% (p = 0.687), 6.3% (p = 0.687); 75% responder rates: 15.3% (p = 0.989), 12.5% (p = 0.989), 14.3% (p = 0.989) versus 13.0%; 50% responder rates: 35.6% (p = 0.425), 33.9% (p = 0.625), and 42.9% (p = 0.125) versus 27.8%; TEAEs were reported by 80.0% (48/60), 78.9% (45/57), 83.1% (49/59) versus 67.3% (37/55). Significance In both trials, the primary outcomes did not reach statistical significance in any PSL dose group compared with placebo. PSL was generally well tolerated, and no new safety signals were identified. |
| Databáze: | OpenAIRE |
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